pilot immunotherapy study with letetresgene autoleucel (lete-cel, gsk3377794)t-cells in new york esophageal squamous cell carcinoma-1 (ny-eso-1)/ lage-1a-positive advanced non-small cell lung cancer (nsclc) either alone or in combination with pembrolizumab

Conditions: Neoplasms

Summary: this trial will evaluate safety and tolerability of letetresgene autoleucel (gsk3377794) with or without pembrolizumab in participants with non-small cell lung cancer.

new york esophageal squamous cell carcinoma-1 (ny-eso-1) and lage-1a antigens are tumor-associated proteins that have been found in several tumor types. clinical trials using adoptively transferred t- cells directed against ny-eso-1/lage-1a have shown objective responses. letetresgene autoleucel (gsk3377794) is the first generation of ny-eso-1 specific t-cell receptor (tcr) engineered t-cells. this is a multi-arm, open-label study of letetresgene autoleucel (lete-cel, gsk3377794) in human leukocyte antigen (hla)-a\*02:01, hla-a\*02:05 and/or hla-a\*02:06 positive adults whose tumors express ny-eso-1 and/or lage-1a. this study will enroll participants who have unresectable stage iiib or stage iv nsclc.

Eligibility criteria:
inclusion criteria: * age \>=18 years on the day of signing informed consent. * histologically or cytologically diagnosed unresectable stage iiib or stage iv nsclc. * eastern cooperative oncology group (ecog) performance status of 0 or 1. * participant is positive for any of the following alleles: human leukocyte antigen (hla)-a\*02:01, hla-a\*02:05, and a) or hla-a\*02:06 by a validated test. * participant's tumor meets the pre-defined threshold for expression of ny-eso-1 and/or lage-1a. * adequate organ function and blood cell counts, as defined in the protocol. * predicted life expectancy that is \>=24 weeks from leukapheresis. * left ventricular ejection fraction \>=45%. * prior therapies prior to lymphodepletion: a) all participants with nsclc lacking actionable genetic aberrations, per national comprehensive cancer network (nccn) guidelines (arms a and b), need to have received at least one line of programmed death protein 1/programmed death protein 1 ligand (pd-1/pd-l1) checkpoint blockade therapy. for participants in the metastatic setting, pd-1/pd-l1 checkpoint blockade therapy must have been received either alone, in combination or sequentially with platinum-containing chemotherapy. or b) all participants with nsclc with actionable genetic aberrations, per nccn guidelines (arm c only), should have received appropriate targeted therapy following nccn or equivalent country-level guidelines. * disease progression at time of treatment, as defined in the protocol. * measurable disease at time of treatment per response evaluation criteria in solid tumors (recist) version 1.1 as assessed by local site investigator/radiology. exclusion criteria: * prior treatment: previous treatment with genetically engineered ny-eso-1-specific t-cells. previous ny-eso-1 vaccine or ny-eso-1 targeting antibody. prior gene therapy using an integrating vector. * prior allogeneic/autologous bone marrow or solid organ transplantation. * history of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, dimethylsulfoxide (dmso) or other agents used in the study. * severe hypersensitivity (\>= grade 3) to pembrolizumab and/or any of its excipients. * active autoimmune disease that has required systemic treatment in past 2 years. * history of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments. * uncontrolled intercurrent illness. * participant has active infection with human immunodeficiency virus (hiv), hepatitis b virus (hbv), hepatitis c virus (hcv), epstein barr virus (ebv), cytomegalovirus (cmv), syphilis, or human t lymphotropic virus (htlv), as defined in protocol. * known psychiatric or substance abuse disorders. * symptomatic or untreated central nervous system (cns) metastases. * radiotherapy that involves the lung (percentage of normal lung receiving at least 20 gray \[gy\] during radiotherapy \[v20\] exceeding 30% lung volume or mean heart dose \>20 gy) within 3 months or radiotherapy (including but not limited to palliative radiotherapy) to lung/mediastinum with v20 less than 30% lung volume and with mean heart dose \<=20 gy within 4 weeks (+/- 3 days). * radiotherapy of \>=50 gy to a significant volume of the pelvis, long bones or spine, or a cumulative dose of radiation that, in the investigator's opinion would predispose participants to prolonged cytopenia after lymphodepletion. * all of the participant's measurable lesions have been irradiated within 3 months before lymphodepletion. * other protocol-defined inclusion/exclusion criteria may apply.

Keywords: gsk3377794 pembrolizumab t cell receptors adoptive t-cell therapy non-small cell lung cancer immuno-oncology ny-eso-1 lage-1a leukapheresis letetresgene autoleucel